In the medical literature the less precise term, "impotence" has been replaced by the term "erectile dysfunction." This term has been defined by the National Institutes of Health as the inability of the male to attain and maintain erection of the penis sufficient to permit satisfactory sexual intercourse. J. Am. Med. Assoc., 270(1):83-90 (1993). Because adequate arterial blood supply is critical for erection, any disorder that impairs blood flow may be implicated in the etiology of erectile failure. Erectile dysfunction affects millions of men and, although generally regarded as a benign disorder, has a profound impact on their quality of life. It is recognized, however, that in many men psychological desire, orgasmic capacity, and ejaculatory capacity are intact even in the presence of erectile dysfunction.
Etiological factors for erectile disorders have been categorized as psychogenic or organic in origin. Organic factors include those of a neurogenic origin and those of a vasculogenic origin. Neurogenic factors include, for example, lesions of the somatic nervous pathways which may impair reflexogenic erections and interrupt tactile sensations needed to maintain erections, and spinal cord lesions which, depending upon their location and severity, may produce varying degrees of erectile failure.
Psychogenic factors for erectile dysfunction include such processes as depression, anxiety, and relationship problems which can impair erectile functioning by reducing erotic focus or otherwise reducing awareness of sensory experience. This may lead to an inability to initiate or maintain an erection.
Vasculogenic risk factors include factors which affect blood flow and include cigarette smoking, diabetes mellitus, hypertension, vascular disease, high levels of serum cholesterol, low levels of high-density lipoprotein (HDL), and other chronic disease conditions such as arthritis. The Massachusetts Male Aging Study (MMAS, as reported by H. A. Feldman, et al., J. Urol., 151: 54-61 (1994) found, for example, that the age-adjusted probability of complete erectile dysfunction was three times greater in subjects reporting treated diabetes than in those without diabetes. While there is some disagreement as to which of the many aspects of diabetes is the direct cause of erectile dysfunction, vascular disease is most frequently cited.
The MMAS also found a significant correlation between erectile dysfunction and heart disease with two of its associated risk factors, hypertension and low serum high density lipoprotein (HDL). It has been reported that 8-10% of all untreated hypertensive patients are impotent at the time they are diagnosed with hypertension. The association of erectile dysfunction with vascular disease in the literature is strong, with impairments in the hemodynamics of erection demonstrated in patients with myocardial infarction, coronary bypass surgery, cerebrovascular accidents, and peripheral vascular disease. The MMAS also found cigarette smoking to be an independent risk factor for vasculogenic erectile dysfunction, with cigarette smoking found to exacerbate the risk of erectile dysfunction associated with cardiovascular diseases.
The treatment of erectile dysfunction varies, depending upon the root causes of the condition in a particular patient. The mode of treatment may involve the use psychotherapeutic, surgical, mechanical, or pharmacotherapeutic methodology. Psychotherapy and/or behavioral therapy are often useful for some patients with erectile dysfunction with no obvious organic cause (psychogenic). Venous ligation is effective in the treatment of patients who have difficulty maintaining an erection due to demonstrated venous leakage from the corpus cavernosa. Vacuum constriction devices are sometimes effective in generating and maintaining erections in patients with erectile dysfunction, and semi-rigid, malleable, or inflatable penile prostheses are available for patients who fail or refuse other forms of therapy.
Pharmacologic agents which have been used in the treatment of erectile dysfunction include vasodilators which are injected directly into the body of the penis, as well as orally administered agents. The most effective and well-studied of the injectable vasodilators are papaverine hydrochloride, phentolamine, and alprostadil, used singly or in combination. However, use of penile vasodilators can be problematic in patients who cannot tolerate transient hypotension. Orally administered agents include yohimbine, bromocriptine, fluoxetine, trazadone, trental, sildenafil, phentolamine, and extracts of ginkgoacea biloba.
U.S. Pat. No. 5,770,606 discloses the sub-lingual administration of apomorphine for the treatment of psychogenic erectile dysfunction in males. Apomorphine, a derivative of morphine, was first evaluated for use as a pharmacologic agent as an emetic in 1869. In the first half of the 20.sup.th century, apomorphine was used as a sedative for psychiatric disturbances and as a behavior-altering agent for alcoholics and addicts. By 1967, the dopaminergic effects of apomorphine were realized, and the compound underwent intensive evaluation for the treatment of Parkinsonism. Since that time, apomorphine has been classified as a selective dopamine receptor agonist that stimulates the central nervous system producing an arousal response manifested by yawning and penile erection in animals and man.